Genomic survey and comprehensive analysis of acquired vancomycin and linezolid resistance in enterococci isolated from dogs and cats.

Enterococcus species are clinically important opportunistic pathogens capable of acquiring and disseminating antimicrobial resistance (AMR). Although vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci (LRE) are increasingly reported in human medicine, their prevalence and genomic features in companion animals remain poorly characterized. This study investigated the global distribution and genetic traits of acquired vancomycin and linezolid resistance determinants in enterococci from dogs and cats. Among 32,971 genomes analyzed, 34 carried vanA, optrA, poxtA, and/or cfr. VanA-positive strains were predominantly Enterococcus faecium and were identified in Europe, Oceania, Asia, and South America between 1995 and 2021. All harbored the vanHAX cluster, mainly associated with Tn1546-like transposons. Transferable oxazolidinone resistance genes were identified in 25 strains, mostly Enterococcus faecalis, recovered exclusively from China and the United States between 2015 and 2023. The optrA gene (OptrA variants RDK and KLDK, defined by specific amino acid substitutions) and optrA-fexA genetic context predominated, whereas poxtA and cfr were each identified in a single isolate. One E. faecium strain co-harbored optrA and poxtA. VRE and LRE populations displayed high sequence type diversity, including lineages previously reported in human healthcare settings (ST78 and ST80) and livestock (ST27), as well as novel lineages (ST3090, ST3091, and ST2180). Genomic analyses and literature data indicate that VRE and LRE in dogs and cats remain uncommon but are globally distributed and associated with diverse lineages and mobile resistance platforms shared across human, animal, and environmental reservoirs. Enhanced surveillance is needed to better understand the epidemiology and dissemination of these clinically relevant resistance determinants.